The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

Chatzileontiadou, D.S.M.; Sloane, Hannah; Nguyen, Andrea; Gras, Stéphanie; Grant, Emma J.

doi:10.3390/ijms22010073

Cited by 62 publications

(47 citation statements)

References 253 publications

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“…SCAF5 stimulated NO production in macrophages, and these results were corroborated by RT-qPCR analysis which showed a two-fold increase in iNOS mRNA expression. Increases in the expression of iNOS and SCAF5-induced NO observed in this study are indicative of a T H 1-mediated response [29]. There are several T H cell subsets classi ed based on their unique cytokine pro les and functions [30] ,with the T H 1-mediated response contributing towards microbicidal activity (i.e., NO production and phagocytosis), which are highly effective in clearing intracellular pathogens (e.g., bacteria and viruses) compared with the T H 2 phenotype which is implicated in less desirable hypersensitivity reactions [31].…”

Section: Discussionsupporting

confidence: 58%

Extracts of Sida Cordifolia Contain Polysaccharides Possessing Immunomodulatory Activity and Rosmarinic Acid Compounds With Antibacterial Activity

Iqbal

Wright

Jones

et al. 2021

Preprint

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Background:The overuse of antibiotics has led to increased antimicrobial resistance, but plant-derived biological response modifiers represent a potential alternative to these drugs. This investigation examined the immunomodulatory and antibacterial activities of Sida cordifolia (used in ethnomedicinal systems to treat infectious disease). Methods:Successive extractions were performed from the roots of these plants in hexane, chloroform, methanol and water. Immunomodulatory activity was determined in a series of experiments measuring the responses of splenocytes, macrophages and an in vivo model of innate immunity (Galleria mellonella). Antibacterial activity was assessed by determining minimum inhibitory/bactericidal concentrations (MIC/MBCs) for various Gram-positive and Gram-negative bacterial strains. Results: Immunomodulatory activity was confined to the aqueous extract, and further fractionation and biochemical analysis yielded a highly potent polysaccharide-enriched fraction (SCAF5). SCAF5 is a complex mixture of different polysaccharides with multiple immunomodulatory effects including immune cell proliferation, antibody secretion, phagocytosis, nitric oxide production, and increased expression of pro-inflammatory cytokines. Furthermore, Galleria mellonella pre-treated with SCAF5 produced more haemocytes and were more resistant (P<0.001) to infection with methicillin-resistant Staphylococcus aureus (MRSA) with a 98% reduction in bacterial load in pre-treated larvae compared to the negative control. The antibacterial activity of Sida cordifolia was confined to the methanolic fraction. Extensive fractionation identified two compounds, rosmarinic acid and its 4-O-β-d-glucoside derivative, which had potent activity against Gram-positive antibiotic-resistant bacteria, including MRSA. Conclusions:Sida cordifolia counters bacterial infections through a dual mechanism, and immunomodulatory polysaccharides from this plant should be isolated and characterised to realise their potential as anti-infective agents. Such properties could be developed as an antibiotic alternative (1) in the clinic and (2) alternative growth promoter for the agri-food industry.

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Section: Discussionsupporting

confidence: 58%

Extracts of Sida Cordifolia Contain Polysaccharides Possessing Immunomodulatory Activity and Rosmarinic Acid Compounds With Antibacterial Activity

Iqbal

Wright

Jones

et al. 2021

Preprint

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“…In addition to IFNγ, Th1 cells are also capable of producing IL-2, IL-10 and TNF-α, many of which participate in the inflammatory process ( 134 , 135 ). Th2 cells, on the other hand, mainly assist in the humoral immune response ( 136 ). Cytokines secreted by Th2 cells include IL-4, IL-5 and IL-13, which facilitate the isotope switching of antibodies, mucus secretion and eosinophilia ( 137 ).…”

Section: Discussionmentioning

confidence: 99%

“…Another intriguing finding of our study is that the proportions of Tfh cells and B cells are significantly elevated in the peripheral blood of AS patients. Both Tfh cells and B cells participate in humoral immunity ( 136 ). After migrating to the B cell follicles, CD40L expressed on the cell surface of Tfh cells may interact with the CD40 on B cells serving as a stimulus signal, thereby facilitating the formation of germinal center, differentiation of B cells and ultimately the production of antibodies ( 63 , 138 ).…”

Section: Discussionmentioning

confidence: 99%

Imbalance of Peripheral Lymphocyte Subsets in Patients With Ankylosing Spondylitis: A Meta-Analysis

Liu

Lin

et al. 2021

Front. Immunol.

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Ankylosing spondylitis is a complicated consequence of genetic predisposition and environmental factors. Enthesitis is believed to be the hallmark of ankylosing spondylitis, and the chronic inflammatory state of this disease is perpetuated by the disturbances of both the innate immune system and the acquired immune system. To clarify the alteration of immune system in patients with AS, we conducted a meta-analysis concerning the proportions of major lymphocyte subsets in the peripheral blood of AS patients. We systematically searched PubMed and China National Knowledge Infrastructure (CNKI) for articles related to this subject. A total of 95 articles involving 4,020 AS patients and 3,065 healthy controls were included in the analysis. This meta-analysis is performed on R platform using R package “meta”, and Egger’s tests were used to determine the presence of publication bias. Results showed that the percentages of T cells, NK cells and NKT cells were not significantly different between AS patients and healthy controls, but B cells were significantly increased. Among the subsets of T cells, the proportions of CD4+ T cells, Th17 cells, Tfh cells as well as Th1/Th2 ratio were significantly increased, while Tregs were significantly decreased. Subgroup analysis showed that the proportions of Th17 among both PBMCs, T cells and CD4+ T cells were significantly elevated, while Tregs were only significantly lower in PBMCs. Subgroup analysis also demonstrated that Tregs defined by “CD4+CD25+FoxP3+”, “CD4+CD25+CD127low”or “CD4+CD25+CD127-”were significantly downregulated, indicating that the selection of markers could be critical. Further study is warranted in order to elucidate the complicated interactions between different lymphocyte subsets in AS patients. This study implied that the disequilibrium between Th17 and Tregs, as well as between Th1 and Th2 could contribute to the pathogenesis of ankylosing spondylitis, further cementing the understanding that ankylosing spondylitis is a consequence of disrupted balance of innate immune system and acquired immune system.

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“…CD4 + T cells mainly include Th1, Th2, Th17, Th9, Th22, follicular helper T (Tfh) cells and regulatory T (Treg) cells (1)(2)(3)(4), and they were initially divided into two categories: Th1 and Th2 cells (5). This classification does not explain the pathogenesis of certain diseases; for example, neutralizing or eliminating IL-12 or Th1 cells and the cytokine IFN-g could not prevent or alleviate experimental autoimmune encephalomyelitis (EAE) and collagen-induced arthritis (CIA); however, the discovery of Th17 cells explains this paradox.…”

Section: Introductionmentioning

confidence: 99%

Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

et al. 2021

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Upon antigenic stimulation, naïve CD4+T cells differentiate into different subsets and secrete various cytokines to exert biological effects. Th22 cells, a newly identified CD4+T cell subset,are distinct from the Th1, Th2 and Th17 subsets. Th22 cells secrete certain cytokines such as IL-22, IL-13 and TNF-α, but not others, such as IL-17, IL-4, or interferon-γ (IFN-γ), and they express chemokine receptors CCR4, CCR6 and CCR10. Th22 cells were initially found to play a role in skin inflammatory diseases, but recent studies have demonstrated their involvement in the development of various autoimmune diseases. Here, we review research advances in the origin, characteristics and effector mechanisms of Th22 cells, with an emphasis on the role of Th22 cells and their main effector cytokine IL-22 in the pathogenesis of autoimmune diseases. The findings presented here may facilitate the development of new therapeutic strategies for targeting these diseases.

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The Many Faces of CD4+ T Cells: Immunological and Structural Characteristics

Cited by 62 publications

References 253 publications

Extracts of Sida Cordifolia Contain Polysaccharides Possessing Immunomodulatory Activity and Rosmarinic Acid Compounds With Antibacterial Activity

Extracts of Sida Cordifolia Contain Polysaccharides Possessing Immunomodulatory Activity and Rosmarinic Acid Compounds With Antibacterial Activity

Imbalance of Peripheral Lymphocyte Subsets in Patients With Ankylosing Spondylitis: A Meta-Analysis

Role of Th22 Cells in the Pathogenesis of Autoimmune Diseases

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